Is CEP164 p.Arg1122Pro (c.3365G>C) pathogenic?

CEP164 p.Arg1122Pro (c.3365G>C) is classified Uncertain significance in CEP164 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-11-13). AlphaMissense: ambiguous (0.4946); Very rare (popmax 0.00801%, afr); Associated with Inborn genetic diseases.

What condition is associated with CEP164 p.Arg1122Pro (c.3365G>C)?

CEP164 p.Arg1122Pro (c.3365G>C) is associated with Inborn genetic diseases, nephronophthisis 15 (ClinVar).

How common is CEP164 p.Arg1122Pro (c.3365G>C) in the general population?

CEP164 p.Arg1122Pro (c.3365G>C) is very rare (popmax 0.00801%, afr) (gnomAD).

What do computational predictors say about CEP164 p.Arg1122Pro (c.3365G>C)?

AlphaMissense predicts ambiguous (score 0.4946) — an in-silico prediction, not a clinical call.

CEP164 p.Arg1122Pro

c.3365G>C · rs144910893 · VCV863950

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

ambiguous

0.4946 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00801%, afr)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4946	ambiguous
REVEL	0.135	moderately benign-leaning
SaProt	LLR -11.98	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.35	GERP -2.2
Regional constraint	o/e 0.97	unconstrained · MANE · 74 kb · p 0.19 · regional, not allelic
Overall
CADD	15.69	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00801% African / African-American · 6/74,936 alleles

Filtering AF 0.00347% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00228%

Overall 0.000434% 7/1,614,020 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00801%	12,489
Remaining individualsnot grpmax-eligible	0.0016%	62,484

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: CEP164
Protein: p.Arg1122Pro
Coding: c.3365G>C
MANE Select: NM_014956
dbSNP: rs144910893
Type: single nucleotide variant
Location: chr11:117397177 (GRCh38)
Gene constraint: LOEUF 1.009 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 63.08 · 4 PDB

Full CEP164 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: nephronophthisis 15

Similar variants

CEP164 p.Arg1122Cys Benign/Likely benign ★★ same residue
CEP164 p.Arg1122His Likely benign ★★ same residue
CEP164 c.1234-2A>T Likely pathogenic ★★ same condition
CEP164 c.1724+1G>A Likely pathogenic ★★ same condition
CEP164 c.1934+1G>A Likely pathogenic ★★ same condition
CEP164 c.2361+1G>A Likely pathogenic ★★ same condition
CEP164 c.2493+1G>A Likely pathogenic ★★ same condition
CEP164 c.2914-1G>C Likely pathogenic ★★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/cep164-p-arg1122pro (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown